研究动态
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鸡糖原合成酶激酶3β在DF-1细胞中抑制先天免疫反应并增强禽白血病病毒复制。

Chicken Glycogen Synthase Kinase 3β Suppresses Innate Immune Responses and Enhances Avian Leukosis Virus Replication in DF-1 Cells.

发表日期:2023 Mar 30
作者: Zhouhao Cui, Bei Weng, Yongxiu Yao, Hongxia Shao, Jianqiang Ye, Aijian Qin, Kun Qian
来源: Microbiology Spectrum

摘要:

Glycogen synthase kinase 3β(GSK3β)是一种广泛分布的多功能丝氨酸/苏氨酸激酶。在哺乳动物中,GSK3β调节着重要的生命活动,如促炎反应、抗炎反应、免疫和癌症发展。然而,鸡GSK3β(chGSK3β)的生物学功能仍然未知。在本研究中,首次克隆和分析了chGSK3β的全长cDNA。特定病原体自由1日龄禽鸟中鸡chGSK3β的绝对定量表明它在所有组织中广泛表达,在脑中最高,在胰腺中最低。在DF-1细胞中过量表达chGSK3β显著降低了干扰素β(IFN-β)、IFN调节因子7(IRF7)、Toll样受体3(TLR3)、黑色素瘤分化相关蛋白5(MDA5)、MX-1、蛋白激酶R(PKR)和寡腺苷酸合成酶样(OASL)的基因表达水平,同时促进家禽白血病病毒J亚组(ALV-J)的复制。相反,当使用小干扰RNA(siRNA)靶向降低chGSK3β表达时,本研究检测到大多数基因的水平增加,这也抑制了ALV-J的复制。这些结果表明chGSK3β在DF-1细胞的抗病毒先天免疫反应中发挥着重要作用,进一步研究其生物学功能将具有重要价值。重要性:GSK3β调节哺乳动物的许多生命活动。最近的研究发现,chGSK3β参与调节DF-1细胞的抗病毒先天免疫,并可正向调节ALV-J的复制。这些结果为chGSK3β的生物功能和ALV-J的病毒-宿主相互作用提供了新的见解。此外,该研究为进一步研究家禽GSK3的功能提供了基础。
Glycogen synthase kinase 3β (GSK3β) is a widely distributed multifunctional serine/threonine kinase. In mammals, GSK3β regulates important life activities such as proinflammatory response, anti-inflammatory response, immunity, and cancer development. However, the biological functions of chicken GSK3β (chGSK3β) are still unknown. In the present study, the full-length cDNA of chGSK3β was first cloned and analyzed. Absolute quantification of chicken chGSK3β in 1-day-old specific-pathogen-free birds has shown that it is widely expressed in all tissues, with the highest level in brain and the lowest level in pancreas. Overexpression of chGSK3β in DF-1 cells significantly decreased the gene expression levels of interferon beta (IFN-β), IFN regulatory factor 7 (IRF7), Toll-like receptor 3 (TLR3), melanoma differentiation-associated protein 5 (MDA5), MX-1, protein kinase R (PKR), and oligoadenylate synthase-like (OASL), while promoting the replication of avian leukosis virus subgroup J (ALV-J). Conversely, levels of most of the genes detected in this study were increased when chGSK3β expression was knocked down using small interfering RNA (siRNA), which also inhibited the replication of ALV-J. These results suggest that chGSK3β plays an important role in the antiviral innate immune response in DF-1 cells, and it will be valuable to carry out further studies on the biological functions of chGSK3β. IMPORTANCE GSK3β regulates many life activities in mammals. Recent studies revealed that chGSK3β was involved in regulating antiviral innate immunity in DF-1 cells and also could positively regulate ALV-J replication. These results provide new insights into the biofunction of chGSK3β and the virus-host interactions of ALV-J. In addition, this study provides a basis for further research on the function of GSK3 in poultry.